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Year 2 Medicine > Mucosal Immunology 2 > Flashcards

Mucosal Immunology 2 Flashcards

1
Q

What is the mesentery?

A

Mesentery: double fold of peritoneum that attaches the gut to the posterior abdominal wall. - since 2021 has been considered an organ in it’s own right

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2
Q

Mesenteric lymph nodes are located at the … of the mesentery and collect lymph, cells and antigens from the intestinal …

A

Mesenteric lymph nodes are located at the base of the mesentery and collect lymph, cells and antigens from the intestinal mucosa.

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3
Q

What is the main site for oral tolerance induction?

A

mesenteric lymph nodes

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4
Q

What is oral tolerance?

A

avoidance of an immune response to foodstuffs (and other matter).

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5
Q

Oral tolerance induction as a … option in allergy

A

Oral tolerance induction as a therapeutic option in allergy

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6
Q

Oral tolerance induction as a therapeutic option in …

A

Oral tolerance induction as a therapeutic option in allergy

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7
Q

Mesenteric Lymph Nodes (MLN): overview (2)

  • Location of mesenteric lymph nodes in relation to small intestine
  • What is the main function of the SI?
A

Main function - complete digestion of food and absorb nutrients.

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8
Q

Mesenteric Lymph Nodes (MLN): overview (3)​

  • Location of mesenteric lymph nodes in relation to large intestine
  • What is the main role of the colon? (Large intestine?)
A
  • absorbing water and electrolytes, producing and absorbing vitamins, and forming and propelling faeces toward the rectum for elimination
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9
Q

Mesenteric Lymph Nodes (MLN): traffic (4)

  • MLN drain lymph from intestinal …
  • Naïve B-cells and T-cells arriving via … endothelial … will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
  • They will return to effector sites in the gut (‘homing’)
A
  • MLN drain lymph from intestinal mucosa
  • Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
  • They will return to effector sites in the gut (‘homing’)
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10
Q

Mesenteric Lymph Nodes (MLN): traffic (4)

  • MLN drain lymph from intestinal mucosa
  • Naïve B-cells and T-cells arriving via high endothelial venules will travel from … patches (induction sites) via MLN to the thoracic duct and blood stream
  • They will return to … sites in the gut (‘homing’)
A
  • MLN drain lymph from intestinal mucosa
  • Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
  • They will return to effector sites in the gut (‘homing’)
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11
Q

Mesenteric Lymph Nodes (MLN): traffic (4)

  • MLN drain lymph from intestinal mucosa
  • Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
  • They will return to effector sites in the gut (‘…’)
A
  • MLN drain lymph from intestinal mucosa
  • Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
  • They will return to effector sites in the gut (‘homing’)
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12
Q

Mesenteric Lymph Nodes (MLN): traffic (5)

  • Food antigens (in particular …) will pass through lymph but also reach the … through capillaries and ultimately the portal vein.
  • Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the portal vein (e.g. LPS)
  • Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are … (along with inflammation).
A
  • Food antigens (in particular fats) will pass through lymph but also reach the liver through capillaries and ultimately the portal vein.
  • Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the portal vein (e.g. LPS)
  • Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are raised (along with inflammation).
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13
Q

Mesenteric Lymph Nodes (MLN): traffic (5)

  • Food antigens (in particular fats) will pass through lymph but also reach the liver through capillaries and ultimately the … …
  • Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the … … (e.g. LPS)
  • Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are raised (along with inflammation).
A
  • Food antigens (in particular fats) will pass through lymph but also reach the liver through capillaries and ultimately the portal vein.
  • Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the portal vein (e.g. LPS)
  • Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are raised (along with inflammation).
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14
Q

Lamina propria and intraepithelial lymphocyte compartment (1)

  • Intraepithelial lymphocytes (IEL) are situated in the … portion of the epithelium.
  • Features of IEL include:
    • … shape
    • Long extensions in close contact with neighboring epithelial cells
    • Occurrence in variable numbers along the gut
    • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​
A
  • Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
  • Features of IEL include:
    • Irregular shape
    • Long extensions in close contact with neighboring epithelial cells
    • Occurrence in variable numbers along the gut
    • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​
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15
Q

Lamina propria and intraepithelial lymphocyte compartment (1)

  • Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
  • Features of IEL include:
    • Irregular shape
    • Long … in close contact with neighboring epithelial cells
    • Occurrence in … numbers along the gut
    • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​
A
  • Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
  • Features of IEL include:
    • Irregular shape
    • Long extensions in close contact with neighboring epithelial cells
    • Occurrence in variable numbers along the gut
    • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​
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16
Q

Lamina propria and intraepithelial lymphocyte compartment (1)

  • Intraepithelial lymphocytes (IEL) are situated in the … portion of the epithelium.
  • Features of IEL include:
    • Irregular shape
    • Long extensions in close contact with neighboring epithelial cells
    • Occurrence in variable numbers along the gut
    • Mixed with … (up to 12% in intraepithelial cell preparations) ​
A
  • Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
  • Features of IEL include:
    • Irregular shape
    • Long extensions in close contact with neighboring epithelial cells
    • Occurrence in variable numbers along the gut
    • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​
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17
Q

Lamina propria and intraepithelial lymphocyte compartment (2)

  • Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
    • …-… … T-cells
      • TCRab+CD8ab+
      • TCRab+ CD8aa+
      • TCRab+CD4
    • Innate-like and innate lymphocytes including
      • mucosa-associated invariant T-cells cells (MAIT) ,
      • invariant
      • NK-T-cells,
      • g/d T-cells,
      • NK-cells
A
  • Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
    • Tissue-resident memory T-cells
      • TCRab+CD8ab+
      • TCRab+ CD8aa+
      • TCRab+CD4
    • Innate-like and innate lymphocytes including
      • mucosa-associated invariant T-cells cells (MAIT) ,
      • invariant
      • NK-T-cells,
      • g/d T-cells,
      • NK-cells
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18
Q

Lamina propria and intraepithelial lymphocyte compartment (2)

  • Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
    • Tissue-resident memory T-cells
      • TCRab+CD8ab+
      • TCRab+ CD8aa+
      • TCRab+CD4
    • …-like and … lymphocytes including
      • mucosa-associated invariant T-cells cells (MAIT) ,
      • invariant
      • NK-T-cells,
      • g/d T-cells,
      • NK-cells
A
  • Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
    • Tissue-resident memory T-cells
      • TCRab+CD8ab+
      • TCRab+ CD8aa+
      • TCRab+CD4
    • Innate-like and innate lymphocytes including
      • mucosa-associated invariant T-cells cells (MAIT) ,
      • invariant
      • NK-T-cells,
      • g/d T-cells,
      • NK-cells
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19
Q

Lamina propria and intraepithelial lymphocyte compartment (3)

  • There are also NK cells in the gut, they carry NK-cell receptors
  • Apart from NK-cells some T-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
  • NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
  • … expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
  • Intraepithelial … T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).
A
  • There are also NK cells in the gut, they carry NK-cell receptors
  • Apart from NK-cells some T-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
  • NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
  • IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
  • Intraepithelial CD8 T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).
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20
Q

Lamina propria and intraepithelial lymphocyte compartment (3)

  • There are also NK cells in the …, they carry NK-cell receptors
  • Apart from NK-cells some …-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
  • NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
  • IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
  • Intraepithelial CD8 T-cells produce IFN-g and are important in … … epithelial cells (for example those infected with viruses).
A
  • There are also NK cells in the gut, they carry NK-cell receptors
  • Apart from NK-cells some T-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
  • NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
  • IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
  • Intraepithelial CD8 T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).
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21
Q

… expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)

A

IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)

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22
Q

Intraepithelial … …-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).

A

Intraepithelial CD8 T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).

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23
Q

NKG2D can bind to stress receptors expressed on damaged gut epithelial cells,… , or … (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.

A

NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.

24
Q

T-helper-cell differentiation in the gut and the role of dendritic cells (DCs)

  • T-helper cell differentiation is influenced by … cells and …s
  • IL-17 producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
  • The type often found in the gut produces IL-17 and IL-22. These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
  • Classic Th17 cells produce IL-17 and IFN-g and are … They may kill endothelial cells.
A
  • T-helper cell differentiation is influenced by epithelial cells and DCs
  • IL-17 producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
  • The type often found in the gut produces IL-17 and IL-22. These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
  • Classic Th17 cells produce IL-17 and IFN-g and are cytotoxic. They may kill endothelial cells.
25
Q

T-helper-cell differentiation in the gut and the role of dendritic cells (DCs)

  • T-helper cell differentiation is influenced by epithelial cells and DCs
  • IL-… producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
  • The type often found in the gut produces IL-… and IL-… These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
  • Classic Th17 cells produce IL-… and IFN-g and are cytotoxic. They may kill endothelial cells.
A
  • T-helper cell differentiation is influenced by epithelial cells and DCs
  • IL-17 producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
  • The type often found in the gut produces IL-17 and IL-22. These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
  • Classic Th17 cells produce IL-17 and IFN-g and are cytotoxic. They may kill endothelial cells.
26
Q
A
27
Q

T-helper-cell differentiation in the gut and the role of dendritic cells (DCs) (2)

  • T … (…) cells are produced in response to harmless commensals in the presence of retinoic acid and TGF-b, a factor produced by dendritic cells for example.
  • … produce IL-10 among other rcytokines and are crucial in establishing and maintaining tolerance to commensals and food.
  • Dendritic cells (DCs) sit in the lamina propria. Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.
  • The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, HIV infection, and having a basic understanding of these cells is important.
A
  • T regulatory (Treg) cells are produced in response to harmless commensals in the presence of retinoic acid and TGF-b, a factor produced by dendritic cells for example.
  • Tregs produce IL-10 among other rcytokines and are crucial in establishing and maintaining tolerance to commensals and food.
  • Dendritic cells (DCs) sit in the lamina propria. Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.
  • The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, HIV infection, and having a basic understanding of these cells is important.
28
Q

T regulatory (Treg) cells are produced in response to harmless … in the presence of retinoic acid and TGF-…, a factor produced by dendritic cells for example.

A

T regulatory (Treg) cells are produced in response to harmless commensals in the presence of retinoic acid and TGF-b, a factor produced by dendritic cells for example.

29
Q

Tregs produce IL-… among other cytokines and are crucial in establishing and maintaining tolerance to commensals and food.

A
30
Q

Tregs produce IL-10 among other cytokines and are crucial in establishing and maintaining … to commensals and …

A

Tregs produce IL-10 among other cytokines and are crucial in establishing and maintaining tolerance to commensals and food.

31
Q

Dendritic cells (DCs) sit in the … … - Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.

A

Dendritic cells (DCs) sit in the lamina propria. Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.

32
Q

The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, … infection, and having a basic understanding of these cells is important.

A

The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, HIV infection, and having a basic understanding of these cells is important.

33
Q

Lamina propria and intraepithelial lymphocyte compartment (7) - Induction of IL-17 producing and regulatory T-cells.

A
34
Q

Mucosal B cells & IgA (1)

  • IgA is the main antibody in …
  • IgA against food antigens provides immune …
  • IgA activates the complement system only …
  • Secretion of … IgA (coupled by a J chain) depends on a trans-cellular transport mechanism
  • The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.
A
  • IgA is the main antibody in secretions
  • IgA against food antigens provides immune exclusion
  • IgA activates the complement system only weakly
  • Secretion of dimeric IgA (coupled by a J chain) depends on a trans-cellular transport mechanism
  • The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.
35
Q

Mucosal B cells & IgA (2)

  • IgA is the main antibody in secretions
  • IgA against food antigens provides immune exclusion
  • IgA activates the … system only weakly
  • Secretion of dimeric IgA (coupled by a J chain) depends on a …-… transport mechanism
  • The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.
A
  • IgA is the main antibody in secretions
  • IgA against food antigens provides immune exclusion
  • IgA activates the complement system only weakly
  • Secretion of dimeric IgA (coupled by a J chain) depends on a trans-cellular transport mechanism
  • The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.
36
Q

Mucosal B cells & IgA (3)

  • The …-Ig-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
  • It enables the …-… transport of dimeric IgA and also pentameric IgM (‘secretory component’).
  • This mechanism helps … these Immunoglobulins in the mucus where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.
A
  • The Poly-Ig-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
  • It enables the trans-endothelial transport of dimeric IgA and also pentameric IgM (‘secretory component’).
  • This mechanism helps enriching these Immunoglobulins in the mucus where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.
37
Q

Mucosal B cells & IgA (3)

  • The …-…-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
  • It enables the trans-… transport of dimeric IgA and also pentameric IgM (‘secretory component’).
  • This mechanism helps enriching these … in the … where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.
A
  • The Poly-Ig-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
  • It enables the trans-endothelial transport of dimeric IgA and also pentameric IgM (‘secretory component’).
  • This mechanism helps enriching these Immunoglobulins in the mucus where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.
38
Q

Gut homing of B- and T-cells (1)

  • Homing means that T-cells and B-cells are instructed to return to the … sites adjoining the induction sites where they were …, i.e. first confronted with their ‘cognate’ antigen.
  • Homing happens in … tissues.
  • Gut-homing … of effector lymphocytes are … in the …-associated … tissues where they have undergone differentiation from naive precursors (induction sites).
  • They will home to the same organ, however, to an … site.
A
  • Homing means that T-cells and B-cells are instructed to return to the effector sites adjoining the induction sites where they were primed, i.e. first confronted with their ‘cognate’ antigen.
  • Homing happens in all tissues.
  • Gut-homing properties of effector lymphocytes are imprinted in the gut-associated lymphoid tissues where they have undergone differentiation from naive precursors (induction sites).
  • They will home to the same organ, however, to an effector site.
39
Q

… means that T-cells and B-cells are instructed to return to the effector sites adjoining the induction sites where they were primed, i.e. first confronted with their ‘cognate’ antigen.

A

Homing means that T-cells and B-cells are instructed to return to the effector sites adjoining the induction sites where they were primed, i.e. first confronted with their ‘cognate’ antigen.

40
Q

Gut homing of B- and T-cells (2): the basic principle in a nutshell

  • T-cells primed in a specific … site will be able to re-enter the same tissue at an … site. … molecules on lymphocytes and receptor molecules on endothelial cells function as key & lock
  • T-cells primed in a different specific … site will not be able to enter another tissue at an … site (there may be some overlap)
A
  • T-cells primed in a specific induction site will be able to re-enter the same tissue at an effector site. Adhesion molecules on lymphocytes and receptor molecules on endothelial cells function as key & lock
  • T-cells primed in a different specific induction site will not be able to enter another tissue at an effector site (there may be some overlap)
41
Q

Gut homing of B- and T-cells (2): the basic principle in a nutshell

  • T-cells primed in a specific induction site will be able to re-enter the same tissue at an effector site. Adhesion molecules on lymphocytes and receptor molecules on endothelial cells function as … & …
  • T-cells primed in a different specific induction site will not be able to enter another tissue at an effector site (there may be some overlap)
A
  • T-cells primed in a specific induction site will be able to re-enter the same tissue at an effector site. Adhesion molecules on lymphocytes and receptor molecules on endothelial cells function as key & lock
  • T-cells primed in a different specific induction site will not be able to enter another tissue at an effector site (there may be some overlap)
42
Q

Gut homing of B- and T-cells (4): nutrition and local factors

  • … cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary … … into retinoic acid.
  • Retinoic acid induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
  • Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL
A
  • Dendritic cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary vitamin A into retinoic acid.
  • Retinoic acid induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
  • Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL
43
Q

Gut homing of B- and T-cells (4): nutrition and local factors

  • Dendritic cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary vitamin A into … …
  • This induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
  • Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL
A
  • Dendritic cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary vitamin A into retinoic acid.
  • Retinoic acid induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
  • Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL
44
Q

Gut homing of B and T cells - overview

A
  • (1) Lamina propria dendritic cells capture antigen (Ag) and Vitamin A from the gut lumen. They migrate to a mesenteric lymph node or a PP.
  • (2) When naive B or T-cells are activated by antigen in gut associated lymphatic tissue, they are exposed to retinoic acid (RA) produced by the dendritic cells from Vitamin A .
  • (3) This induces the expression of the chemokine receptor CCR9 and increased expression of integrin α4β7 on primed T-cells. The same mechanisms works for B-cells.
  • (4) The effector lymphocytes then enter the circulation and travel via the lymphatic system, the thoracic duct, and the blood stream back ‘home’ to the gut (‘homing’).
  • (5) The chemokine CCL25 (the ligand for CCR9) and the adhesion molecule MAdCAM (the ligand for α4β7) are displayed on lamina propria venular endothelial cells, allowing access to the homed cells (remember key & lock).
  • (6) This was the journey of a naïve T-cell from entering an induction sites in the gut lymphatic tissue via a HEV to re-entering the gut at an effector site as an antigen-primed effector T-cell. It has now become a lamina propria T-cell.
45
Q

Gut homing of B and T cells - overview

A
  • (1) Lamina propria dendritic cells capture antigen (Ag) and Vitamin A from the gut lumen. They migrate to a mesenteric lymph node or a PP.
  • (2) When naive B or T-cells are activated by antigen in gut associated lymphatic tissue, they are exposed to retinoic acid (RA) produced by the dendritic cells from Vitamin A .
  • (3) This induces the expression of the chemokine receptor CCR9 and increased expression of integrin α4β7 on primed T-cells. The same mechanisms works for B-cells.
  • (4) The effector lymphocytes then enter the circulation and travel via the lymphatic system, the thoracic duct, and the blood stream back ‘home’ to the gut (‘homing’).
  • (5) The chemokine CCL25 (the ligand for CCR9) and the adhesion molecule MAdCAM (the ligand for α4β7) are displayed on lamina propria venular endothelial cells, allowing access to the homed cells (remember key & lock).
  • (6) This was the journey of a naïve T-cell from entering an induction sites in the gut lymphatic tissue via a HEV to re-entering the gut at an effector site as an antigen-primed effector T-cell. It has now become a lamina propria T-cell.
46
Q

Summary of Mucosal Immunology L2 P1

  • Besides Peyer’s patches, lymph nodes at the base of the … play a major role as induction sites in the gut mucosa. They are called … lymph nodes or MLNs. They play a major role in inducing … to foods.
  • Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
  • Intraepithelial CD… T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
  • Intraepithelial CD… T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
  • IL…-producing CD4 T-cells may also produce IL-… in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
  • … T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.
A
  • Besides Peyer’s patches, lymph nodes at the base of the mesentery play a major role as induction sites in the gut mucosa. They are called mesenterial lymph nodes or MLNs. They play a major role in inducing tolerance to foods.
  • Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
  • Intraepithelial CD8 T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
  • Intraepithelial CD4 T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
  • IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
  • Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.
47
Q

Summary of Mucosal Immunology L2 P1

  • Besides Peyer’s patches, lymph nodes at the base of the mesentery play a major role as induction sites in the gut mucosa. They are called mesenterial lymph nodes or MLNs. They play a major role in inducing tolerance to foods.
  • Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
  • Intraepithelial CD8 T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
  • Intraepithelial CD4 T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
  • IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
  • Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.
A
  • Besides Peyer’s patches, lymph nodes at the base of the mesentery play a major role as induction sites in the gut mucosa. They are called mesenterial lymph nodes or MLNs. They play a major role in inducing tolerance to foods.
  • Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
  • Intraepithelial CD8 T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
  • Intraepithelial CD4 T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
  • IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
  • Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.
48
Q

IL17-producing CD4 T-cells may also produce IL-… in addition, a type that stabilizes the … barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is … and can cause tissue damage.

A

IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.

49
Q

… T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

A

Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

50
Q

Summary of Mucosal Immunology L2 P2

  • Mucosal B-cells are located in the … … where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two Ig… molecules joined by a J chain.
  • Secretion of Ig… happens via a … transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
  • Ig… does not efficiently activate complement but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces low affinity Ig… esponses (aimed at immune exclusion).
A
  • Mucosal B-cells are located in the lamina propria where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two IgA molecules joined by a J chain.
  • Secretion of IgA happens via a transcellular transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
  • IgA does not efficiently activate complement but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces low affinity IgA responses (aimed at immune exclusion).
51
Q

Summary of Mucosal Immunology L2 P2

  • Mucosal B-cells are located in the lamina propria where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two IgA molecules joined by a …chain.
  • Secretion of IgA happens via a transcellular transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
  • IgA does not efficiently activate … but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces … affinity IgA responses (aimed at immune exclusion).
A
  • Mucosal B-cells are located in the lamina propria where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two IgA molecules joined by a J chain.
  • Secretion of IgA happens via a transcellular transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
  • IgA does not efficiently activate complement but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces low affinity IgA responses (aimed at immune exclusion).
52
Q

Summary of Mucosal Immunology L2 P3

  • Antigen-primed B-cells and T-cells originate from naïve B- and T-cells whose … pattern is restricted to the blood stream and lymph nodes.
  • These naïve B-cells and T-cells reach PPs and MLN via … endothelial … (HEVs).
  • Following antigen contact (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
  • They finally return to the gut via the blood stream and leave the blood stream via … (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.
A
  • Antigen-primed B-cells and T-cells originate from naïve B- and T-cells whose recirculation pattern is restricted to the blood stream and lymph nodes.
  • These naïve B-cells and T-cells reach PPs and MLN via high endothelial venules (HEVs).
  • Following antigen contact (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
  • They finally return to the gut via the blood stream and leave the blood stream via adhesion (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.
53
Q

Summary of Mucosal Immunology L2 P3

  • Antigen-… B-cells and T-cells originate from naïve B- and T-cells whose recirculation pattern is restricted to the blood stream and lymph nodes.
  • These naïve B-cells and T-cells reach PPs and MLN via high endothelial venules (HEVs).
  • Following antigen … (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
  • They finally return to the gut via the blood stream and leave the blood stream via adhesion (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.
A
  • Antigen-primed B-cells and T-cells originate from naïve B- and T-cells whose recirculation pattern is restricted to the blood stream and lymph nodes.
  • These naïve B-cells and T-cells reach PPs and MLN via high endothelial venules (HEVs).
  • Following antigen contact (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
  • They finally return to the gut via the blood stream and leave the blood stream via adhesion (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.
54
Q

Summary of Mucosal Immunology L2 P4

  • This process is relatively …-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
  • The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during … and will grant access to those cells providing the right ligands (the ‘key’).
  • This … behaviour of lymphocyte populations is referred to as ‘homing’.
  • In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.
A
  • This process is relatively tissue-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
  • The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during inflammation and will grant access to those cells providing the right ligands (the ‘key’).
  • This recirculation behaviour of lymphocyte populations is referred to as ‘homing’.
  • In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.
55
Q

Summary of Mucosal Immunology L2 P4

  • This process is relatively tissue-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
  • The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during inflammation and will grant access to those cells providing the right ligands (the ‘key’).
  • This recirculation behaviour of lymphocyte populations is referred to as ‘…’.
  • In the gut, …. … plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Deficiency decreases gut immunity probably by reducing homing.
A
  • This process is relatively tissue-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
  • The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during inflammation and will grant access to those cells providing the right ligands (the ‘key’).
  • This recirculation behaviour of lymphocyte populations is referred to as ‘homing’.
  • In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.
56
Q

In the gut, … … plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Deficiency decreases gut immunity probably by reducing homing.

A

In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.

Year 2 Medicine (162 decks)

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